6750 testing. The only distinctive, gross signs of toxicity in cockerels were a general listlessness followed either by eventual improvement (250 mg/kg, oral) or ataxia and death (375 mg/kg, oral). Austin elicited no effects in etiolated Triticum coleoptiles.
Acknowledgments. We thank Dr. Dorothy 1. Fennell, NRRL for accession and identification of the fungus. Mention of firm names or trade products does not imply that they are endorsed or recommended by the Department of Agriculture over other firms or similar products not mentioned. Supplementary Material Available: Fractional coordinates (Table I), bond distances (Table II), bond angles (Table III), observed and calculated structure factors (Table IV) and ir, IH NMR, and I3C NMR spectra ( 1 7 pages). Ordering information is given on any current masthead page.
References and Notes (1)
G.Buchi and I. D. Rae in "Aflatoxin", L. A. Goldhlatt, Ed., Academic Press,
New York, N.Y., 1969, pp 55-75. (2) P. S.Steyn, TetrahedronLett, 3331 (1971). (3) R. Vleggaar, P. S. Steyn, and D. W. Nagel, J. Chem. Soc., Perkin Trans. 7, 45 (1974); P. S. Steyn and R. Vleggaar, ibid., 204 (1976). (4) The fungus has been accessioned by the NRRL culture collection as NRRL 6017. ( 5 ) J. W. Kirksey and R. J. Cole, Mycopath. Mycolog. Appl., 54, 291 (1974). (6) The 'H NMR spectrum revealed 32 protons and the l3C NMR spectrum showed 27 carbons. The preliminary unit cell and density calculations suggested mol w i 500. (7) G. Germain, P. Main, and M. M. Woolfson, Acta Crystailogr., Sect. A, 27, 368 (1971). We had to rescaie all special normalized structure factors (MI, Okl, and hM))to 4 0 % of their observed value to obtain a sensible solution. (8) W. R. Busing, K. 0.Martin, and H. A . Levy, "ORFLS, A Fortran Crystallographic Least Squares Program", US. Atomic Energy Commission Report ORNL-TM-305, Oak Ridge National Laboratory, Oak Ridge, Tenn., 1962. (9) C. A. Johnson, "ORTEP-II: A Fortran Thermal-Ellipsoid Plot Program for Crystal Structure Illustrations", US.Atomic Energy Commission Report ORNL-3794. (2d Revision with Supplemental Instructions), Oak Ridge National Laboratory, Oak Ridge, Tenn.. 1970. (10) S.Winstein, P. Carter, F. A. L.Anet, and A. J. R. Bourn, J. Am. Chem. SOC., 87, 5247 (1965). (11) G. Buchi. J. D. White. and G. N. Wogan, J. Am. Chem. Soc., 87, 3484 (1965). (12) A. W. Dunn, R. A. W. Johnstone, 8. Sklarz, and T. J. King, J. Chem. Soc.. Chem. Commun., 270 (1976). (13) Camille and Henry Dreyfus Teacher-Scholar Grant Awardee 19721977.
-
K. K. Chexal, James P. Springer, Jon Clardy* l 3 Ames Laboratory-USERDA and Department of Chemistry Iowa State University Ames, Iowa 5001 1
and acetic acid adsorbed on dehydrated alumina effect various s N 2 displacement reactions and epoxide ring openings under very mild condition^;^ isopropyl alcohol adsorbed on dehydrated alumina can be used for the selective reduction of an aldehyde in the presence of a k e t ~ n eand ; ~ both Collins' reagent supported on Celite,6 and chromic acid intercalated in graphite,' possess distinct advantages (greater selectivity, manipulative convenience) over solutions of the same reagents. Moreover, simple addition of certain supports to a reaction mixture can have a dramatic effect on reaction rate.* The effectiveness of the inorganic support in these reactions appears to be due to a combination of factors-an increase in the effective surface area for reaction; the presence of pores which constrain both substrate and reactant and thus lower the entropy of activation of reaction; and a synergism (for displacement reactions) resulting from bringing electrophile and nucleophile into proximity, while at the same time enhancing the nucleophilicity (and basicity) of the latter.4 We now report that thallium(II1) nitrate (TTN) adsorbed on K-10, a readily available and inexpensive acidic montmorillonite clay,9 is a remarkably effective reagent for the rapid, selective, high yield, room temperature oxidation of a variety of unsaturated organic substrates. The TTN/K-10 reagent is readily prepared by stirring K-10 with a solution of TTN in a mixture of methanol and trimethyl orthoformate followed by evaporation to dryness.I0 The resulting colorless, free-flowing powder can be stored in wellcapped bottles for months without any appreciable loss in activity. All of the oxidations described below were carried out by stirring a suspension of the TTN/K-10 reagent with a solution of the substrate in an inert solvent (heptane, methylene chloride, carbon tetrachloride, toluene, dioxane) until a starch iodide test for thallium(II1) was negative. Products were isolated by removal of the spent reagent system by filtration, washing of the filtrate with aqueous sodium bicarbonate, then water, drying, evaporation of the solvent, and recrystallization or distillation of the crude product. Oxidative rearrangement of alkyl aryl ketones is a particularly smooth reaction. Acetophenones, for instance, are rapidly converted into methyl arylacetates, and yields are excellent (eq l).II Propiophenone and butyrophenone are con-
R=YW/0 R = CH,, 84% R = CH30,92% R = F,&3% (6.W o in CH@Hy'2 R = Br, (cf..%in CH@H)"
Richard J. Cole, Jerry W. Kirksey, Joe W. Dorner National Peanut Research Laboratory-USDA-ARS Dawson, Georgia 31 742 Horace C. Cutler, Billy J. Strawter USDA-ARS Coastal Plain Experiment Station Tifton, Georgia 31 794 Received June 14. 1976
e
verted into methyl a-methyl- and a-ethyl phenylacetate, respectively, under the same reaction conditions (eq 2 ) . These
R = CH,, 9 % R = C2H5,%
Thallium in Organic Synthesis. 44. Oxidative Rearrangements via Oxythallation with Thallium(II1) Nitrate Supported on Clay'J Sir: Considerable recent use has been made of the concept of utilizing reagents or reactants adsorbed on insoluble inorganic supports for organic synthesis. Silver carbonate deposited on Celite is a highly selective and very effective reagent for the oxidation of alcohols to carbonyl c o m p o ~ n d salcohols, ;~ thiols, Journal of the American Chemical Society
/
98:21
results contrast sharply with those obtained using TTN in refluxing acidic methanol; under the latter conditions, for example, propiophenone gives a mixture of methyl a-methylphenylacetate (45%) and a-methoxypropiophenone (32%).'* Oxidations of benzo-fused cycloalkanones with TTN/K- 10 also proceed more cleanly than with T T N in methanol. 1Tetralone is converted to a mixture of more than ten products by TTN in methanol, but with TTN/K-10 a 1:l mixture of methyl indane- 1-carboxylate and 2-methoxy- 1-tetralone is formed (eq 3).
/ October 13, I976
Table I. Comparative Effectiveness of Various Supports for the TTN-Mediated Rearrangement of Acetophenone to Methyl Phen ylacetate
Support AERO 8020 silicaalumina Alcoa F- 1 alumina K- I O montmorillonite clay K-306 montmorillonite clay Florisil Southern bentonite Graphite Davison 135 neutral silica-alumina Amberlyst 15
Reaction timeu
Product distribution Unreacted PhCOC- PhCHZCOH3 OCH3 b
1 min
60
20
20
2 min 5 min
50 99
0 0
5 min
10
70
20
5 min 10 min 30 min 90 min
40 20 25 15
30 80 15 85
30 0 0 0
8h
50
50
0
Time required for complete utilization of TI(II1) as determined by starch iodide paper. Indicates other products are also formed.
COOCH,
0
50%
5%
Oxidative rearrangement of simple olefins such as cyclohexene (eq 4),styrene (eq 5), and 1-phenyl-1-propene (eq 6 )
H=CHCOOCH3 CH3
-
675 1
30 min
,CH(OCH,),
W%
thallation processes, and while the precise reasons for the effectiveness of K-10 in these reactions remain unclear, it appears that supports with a laminar structure, and in particular acidic ones such as K-10, are much more effective than nonacidic sponge-like supports. Moreover, systematic examination of more than 20 different TTN support systems has established that TTN/K-10 is by far the most effective with respect to ease of preparation, rate of reaction, selectivity of oxidation, and general experimental simplicity. Data for the conversion of acetophenone into methyl phenylacetate using TTN deposited on a variety of inorganic and organic supports are listed in Table I, and clearly show that TTN/K-IO is the reagent of choice for this transformation. W e have no clear understanding as yet of the exact physical nature of the TTN/K-10 support system. Reaction of T T N (which is a trihydrate, T1 (ON02)3.3HzO) with trimethyl orthoformate is known to result in removal of the water of hydration from the coordination sphere of the thallium,* and the TTN/K- 10 reagent appears to consist of nonhydrated thallium(II1) nitrate and methanol adsorbed on the surface of the acidic clay. Thus, the dried reagent corresponds approximately by weight to T1 (ON02)3/3CH30H/K-10, and the clay can be washed free of both thallium(II1) nitrate and methanol by treatment with polar solvents such as acetonitrile. One particularly important point about the TTN/K-IO reagent, however, is that under the standard reaction conditions (nonpolar, inert solvents) both the thallium(II1) nitrate on the support and the thallium(1) nitrate which is generated during the reaction are tightly bound to the support throughout the whole of the reaction. Consequently, there is no detectable level (atomic absorption) of contamination of either solvent or product by thallium.I3
References and Notes 92%
CH3
I
91%
is extremely rapid. Although oxidation of cinnamaldehyde and substituted cinnamaldehydes with TTN in methanol gives complex mixtures of products and is of no synthetic utility, the use of TTN/K-10 results in rapid, clean oxidative rearrangement and formation of arylmalondialdehyde tetramethylacetals in excellent yield (eq 7). Cinnamic esters, which are CH(OCH& I
(1) (a) For the previous paper in this series, see E. C. Taylor, R. L. Robey, K.-T. Liu, E. Favre, H. T. Bozimo, R. A. Conley, (2.4. Chiang, A. McKillop, and M. E. Ford, J. Am. Chem. SOC., 98, 3037 (1976). (b) We are indebted to the National Science Foundation (Grant No. MPS72-00427) for partial support of this work. (2) The term "oxythallation" refers to electrophilic attack (usually on a C% bond), by T1(111), accompanied by capture of the resulting carbonium (or thailinium) ion by a nucleophile (gegenion or solvent). The resulting "oxythallated" intermediate Is usually extremely unstable and breaks down spontaneously to product(s). Both mechanistic and synthetic aspects of oxythallation have been discussed in detail in previous papers in this series. (3) See M. Fetizon and P. Mourgues, Tetrahedron, 30,327 (1974). and previous paper in this series. (4) G. H. Posner, D. Z. Rogers, C. M. Kinzig, and G. M. Gurria, Tetrahedron Len.,
3597 (1975). (5) G. H. Posner and A. W. Runquist. Tetrahedron Lett., 3601 (1975). (6) N. H. Andersen and H. Uh. Synth. Commun., 3, 115 (1973). (7) J.-M. Lalancette, G. Rollin. and P. Cumas. Can. J. Chem., 50, 3058 (1972). (8) Unpublished observations by E. C. Taylor, C . 4 . Chiang, and A. McKillop.
(9) Girdler Catalyst K-10, Girdler Chemicals, Inc., Louisville, Ky.
(IO) Detailed directions for the preparation of the TTN/K-10 reagent are as
R1= $= H,5miq86% R, = CH30,R2 = H,5 min, sS% R, =H,&=CH3,15min,83%
unaffected by hot solutions of TTN in methanol, are smoothly oxidized by TTN/K-10 a t room temperature (eq 8). The above conversions clearly demonstrate the relative superiority of TTN/K-10 over TTN/methanol for these oxy-
follows: A 500-ml. round-bottomed flask equipped with a magnetic stirring bar is charged with 125 ml of trimethyl orthoformate and 100 ml of methanol. The mixture is stirred and 49 g (0.1 1 mol) of TTN-SHpO Is added in one portion. Stirring is continued until all of the thallium salt has dissolved (approximately 2 min), and then 110 g of K-10 clay is introduced in one portion through a powder funnel. The reaction is slightly exothermic. The powder funnel is rinsed with 25 ml of methanol and the mixture is stirred for a further 5 min. The flask is then transferred to a rotary evaporator and the excess solvents are removed by distillation under reduced pressure C (15-25 mm)). This is complete in 1.5 h. and (bath temperature 60-70 ' 170 g of lTN/K-10 is obtained as a dry, free-flowing, pale yellow powder. Various batches of the K-10 support material were used, but identical results were obtained in all cases.
Communications to the Editor
6752 ( I 1) Crude yields of chromatographically pure products were uniformly quantitative: the yields reported in this paper are for distilled or recrystallized products. All of the reactions reported herein have been carried out many times with completely reproducible results. (12) A. McKillop, B. P. Swann, and E. C. Taylor, J. Am. Chem. SOC.,95, 3340 (1973). (13) This is true both for 0.1 and 1.0 molar scale reactions.
Edward C. Taylor,* Chih-Shu Chiang Department of Chemistry, Princeton University Princeton, New Jersey 08540 A. McKillop School of Chemical Sciences, University of East Anglia Norwich, England NR4 7TJ J. F. White Emery Industries Cincinnati, Ohio 45232 Received June 1 , 1976
5
0
6a,X=Br b,X=Cl
16
Silver assisted hydrolysis of 1 in aqueous acetone proved more fruitful. In 90% aqueous acetone, 1 reacted eight-ten times slower than 6a, but two-three times faster than 6b. The products isolated from hydrolysis (buffered to allow isolation of 9) are shown in eq 2. YOOH
pOH
93% aqueous > 4
AgC10, (5 equiv) pyridine ( 5 e q u v ) 24 h rcom temp
-
7 72%
Propellanes. 12. A Bridgehead Olefin Transoid in a Six-Membered Ring. Formation of a Stable Cyclopropanone
8
14%
+
+ 9 1.2%
Sir:
A surge of interest' in the production and fate of bridgehead olefins has followed Wiseman's demonstration that these olefins are similar in strain energy and reactivity to their corresponding trans cycloolefins.2 As expected, most work has been limited to cases where the bridgehead double bond is transoid in a ring of 2 7 carbons. While effort has been expended on the synthesis of examples of bridgehead double bonds transoid in six-membered rings,3 no energy comparisons have been possible. We now report data which allow some perspective on the energetics of bridgehead olefin formation. Our approach4 to bridgehead olefins has been through the solvolysis of tricyclic cyclopropyl halides (Le., propellanes); others have also utilized this route.5 An obvious potential precursor for a bridgehead olefin transoid in a six-membered ring is 9,9-dibromo[3.3.1]propellane (9,9-dibromotricyclo[3.3.1.01,5]nonane,1),6 although one would expect relatively more cyclopropyl product than in the earlier cases we reported4b,c(eq 1).
(2)
10 2.1%
Thus the acid mixture of 7 and 8 was the major product. Catalytic hydrogenation (Pd/C, EtOH) gave pure 7.' The olefinic resonance of 8 indicated its presence; the 13C NMR of the mixture showed nine peaks not attributable to 7, including two olefinic carbons (6 151.9, 122.2). The diazomethane-derived esters showed separate resonances at 6 3.62 (7-OCH3) and 6 3.67 (8-OCH3). Cyclopropanone 9, which led to primarily 7 when treated under unbuffered hydrolysis conditions or when shaken with aqueous base, was identified Scheme I
12
Br-Br
1
2 i$OH
Br-OS
Br-YoH
OH
H+
W 4
Solvolysis of 1 (HOAc, 0.012 M NaOAc, 125 "C) proceeded with a rate constant of 3.1 X 10-7s-1, some 6200 times slower than acetolysis of 5. Unfortunately, however, 2 mol of acid was produced, indicating that both bromines had been lost. We pursued this no further, since our experience with 6a indicated we were probably seeing HOAc addition to the cyclopropane ring followed by solvolysis; with 6a, addition took place six times faster than the solvolysis of 1. Journal of the American Chemical Society
/
98:21
/
Cg attack
-H',
-HBr
- 8
15
October 13, 1976
j
~
cleavage
*XH 14
